Diabetes is associated with serious cardiovascular complications that include heart failure. Data from studies conducted in animal models and human subjects suggest that alterations in fatty acid metabolism, independent of atherosclerosis, are involved in the pathogenesis of heart failure in diabetic cardiomyopathy. This study will test the overall hypothesis that excessive myocardial fatty acid delivery and utilization is associated with cardiomyopathy in patients who have type 2 diabetes mellitus. Moreover, we hypothesize that alterations in lipid metabolism can be exploited to develop novel biomarkers for early detection of myocardial lipid exposure and diabetic cardiomyopathy. To test these hypotheses, we will study the relationship between fatty acid metabolism, lipid biomarkers and cardiac function in carefully characterized men and women who span physiological and pathophysiological ranges in insulin sensitivity, plasma lipid biomarkers and cardiac function. The goals of this study are to 1) identify novel plasma biomarkers for early detection and management of diabetic cardiomyopathy;and 2) determine whether manipulations of fatty acid delivery to the heart affect the functional manifestations of diabetic cardiomyopathy. This study will provide a better understanding of the relationship between systemic and myocardial fatty acid metabolism and cardiac function, which could also lead to new strategies for diagnosis, prevention, and treatment of diabetic cardiomyopathy. PUBLIC HEALTH RELEVANCE: Diabetes is associated with serious cardiovascular complications including heart failure that is unrelated to coronary artery disease. Scientific evidence suggests that blood fat levels may play a major role in this complication. Our study will investigate the link between blood fat levels and heart function in adults with type 2 diabetes. Our goal is to develop new blood-based biomarkers of heart disease in diabetics and to provide insight into new therapeutic strategies.